Outgoing Secretary of Homeland Security Janet Napolitano delivers farewell remarks today at the National Press Club in Washington reflecting on four-plus years as a member of President Obama's cabinet. Credit: Mike Levine/ABC News

The outgoing Homeland Security Secretary has a warning for her successor: A massive and "serious" cyber attack on the U.S. homeland is coming, and a natural disaster - the likes of which the nation has never seen - is also likely on its way.

So prepare, and bring "a large bottle of Advil," Janet Napolitano told her yet-to-be-named replacement in a farewell address Tuesday morning.

"Many things still need tending, and my successor will most certainly have a full plate on his or her hands," said Napolitano, who leaves her post next week after more than four years at the helm of the Department of Homeland Security.

Napolitano said she faced "many challenges" during her tenure at DHS, from the H1N1 flu pandemic in 2009 to the Deepwater Horizon oil spill in 2010 and Hurricane Sandy in 2012.

DHS - backed by the Federal Emergency Management Agency, the U.S. Coast Guard and other federal departments and agencies - led the federal government's response to such disasters.

During Napolitano's tenure, her department managed 325 federally declared disasters, and issued more than 60 emergency declarations, she said at the National Press Club in Washington this morning.

Leading a department created in the wake of the Sept. 11, 2001, attacks meant Napolitano has also been at the forefront of the nation's counterterrorism and border enforcement efforts.

After the failed Christmas Day "underwear bombing" attempt in 2009, Napolitano launched a worldwide and "historic" effort - in 190 countries - to enhance passenger screening and counter the threat of "nonmetallic devices" on aircraft, she said.

Transportation Security Administration officers are stationed at airports around the world.

"The lesson is clear: For every attack we experience, every threat we face and every piece of intelligence we come across, we learn," she said. "And we get stronger and more nimble."

During her farewell address, Napolitano, who was governor of Arizona before becoming DHS secretary, touted her department's work on border security and immigration reform.

"Over the past four and a half years, we have invested historic resources to prevent illegal cross-border activity," she said. "Our borders are now better staffed and better protected than at any time in our nation's history, and illegal crossings have dropped to near-40-year-lows."

Napolitano also took a shot at Congress, saying that despite her department's work to "set commonsense immigration enforcement priorities, with a focus on criminals, national security and public safety threats," some lawmakers thwarted administration efforts to codify those priorities into law.

"Congress had a chance to give these so-called Dreamers a way to stay in our country through the Dream Act, but unfortunately, that legislation failed to garner the 60 votes needed for cloture, falling just five votes short, despite strong bipartisan support," Napolitano said.

So last year, Napolitano used her "prosecutorial discretion" to let "young people who meet the strict criteria" temporarily stay in the United States for two years, she said, adding that 430,000 people have already been granted the "deferred action."

At the end of her address Tuesday, Napolitano offered an "Open Letter to My Successor."

Among her pieces of advice: "You will need to forge strong relationships with all of our partners, including Congress, to make sure DHS has the resources it needs to meet our responsibilities to the American people. …

"You also will have to prepare for the increasing likelihood of more weather-related events of a more severe nature as a result of climate change, and continue to build the capacity to respond to potential disasters in far-flung regions of the country occurring at the same time.

"You will need a large bottle of Advil," Napolitano joked.

Still, she said, running DHS is "one of the most rewarding jobs there is."

"What you do here matters to the lives of people all across our great nation, and your decisions affect them in direct, tangible ways," she said. "You make sure their families are safe from terrorist threats, that their local first responders have equipment and training and funding, and that when disaster strikes, people who have lost everything are given food, shelter and hope."

Napolitano surprised many inside Washington when she announced in July that she would be stepping down from her post to become the next president of the University of California system. Beltway rumors suggested Napolitano, a former U.S. attorney in Arizona, was interested in replacing U.S. Attorney General Eric Holder, but he has yet to announce any plans to leave the administration.

Napolitano's departure compounds what the Republican head of the House Homeland Security Committee called a "growing list of unfilled key leadership positions" at DHS, including the posts of deputy secretary, intelligence office chief, U.S. Customs and Border Protection commissioner and Bureau of Immigration and Customs Enforcement director.

The head of the U.S. Citizenship and Immigration Services agency has been nominated to become the deputy secretary, potentially setting up another vacancy.

Rand Beers, the current undersecretary for National Protection and Programs, will serve as acting DHS secretary until a replacement for Napolitano is confirmed by the U.S. Senate.